Mitochondrial DNA Mutation Rates

David A. Plaisted

Recently an attempt was made to estimate the age of the human
race using mitochondrial DNA. This material is inherited
always from mother to children only. By measuring the difference in
mitochondrial DNA among many individuals, the age of the
common maternal ancestor of humanity was estimated at about 200,000
years.

A problem is that rates of mutation are not known by direct
measurement, and are often computed based on assumed evolutionary time
scales. Thus all of these age estimates could be greatly in error.
In fact, many different rates of mutation are quoted by different
biologists.

It shouldn't be very hard explicitly to measure the rate of
mutation of mitochondrial DNA to get a better estimate on
this age. From royal lineages, for example, one could find two
individuals whose most recent common maternal ancestor was, say, 1000
years ago. One could then measure the differences in the
mitochondrial DNA of these individuals to bound its mutation
rate. This scheme is attractive because it does not depend on
radiometric dating or other assumptions about evolution or mutation
rates. It is possible that in 1000 years there would be too little
difference to measure. At least this would still give us some useful
information.

(A project for creation scientists!)

Along this line, some work has recently been done to measure explictly
the rate of substitution in mitochondrial DNA. The reference is
Parsons, Thomas J., et al., A high observed substitution rate in the
human mitochondrial DNA control region, Nature Genetics vol. 15, April
1997, pp. 363-367. The summary follows:

"The rate and pattern of sequence substitutions in the
mitochondrial DNA (mtDNA) control region (CR) is of central
importance to studies of human evolution and to forensic identity
testing. Here, we report a direct measurement of the
intergenerational substitution rate in the human CR. We compared DNA
sequences of two CR hypervariable segments from close maternal
relatives, from 134 independent mtDNA lineages spanning 327
generational events. Ten subsitutions were observed, resulting in an
empirical rate of 1/33 generations, or 2.5/site/Myr. This is roughly
twenty-fold higher than estimates derived from phylogenetic
analyses. This disparity cannot be accounted for simply by
substitutions at mutational hot spots, suggesting additional factors
that produce the discrepancy between very near-term and long-term
apparent rates of sequence divergence. The data also indicate that
extremely rapid segregation of CR sequence variants between
generations is common in humans, with a very small mtDNA bottleneck.
These results have implications for forensic applications and
studies of human evolution." (op. cit. p. 363).

The article also contains this section:

"The observed substitution rate reported here is very high compared to
rates inferred from evolutionary studies. A wide range of CR
substitution rates have been derived from phylogenetic studies,
spanning roughly 0.025-0.26/site/Myr, including confidence
intervals. A study yielding one of the faster estimates gave the
substitution rate of the CR hypervariable regions as 0.118 +-
0.031/site/Myr. Assuming a generation time of 20 years, this
corresponds to ~1/600 generations and an age for the mtDNA MRCA of
133,000 y.a. Thus, our observation of the substitution rate,
2.5/site/Myr, is roughly 20-fold higher than would be predicted from
phylogenetic analyses. Using our empirical rate to calibrate the mtDNA
molecular clock would result in an age of the mtDNA MRCA of only
~6,500 y.a., clearly incompatible with the known age of modern
humans. Even acknowledging that the MRCA of mtDNA may be younger than
the MRCA of modern humans, it remains implausible to explain the known
geographic distribution of mtDNA sequence variation by human migration
that occurred only in the last ~6,500 years.

One biologist explained the young age estimate by assuming essentially
that 19/20 of the mutations in this control region are slightly
harmful and eventually will be eliminated from the population. This
seems unlikely, because this region tends to vary a lot and therefore
probably has little function. In addition, the selective disadvantage
of these 19/20 of the mutations would have to be about 1/300 or higher
in order to avoid producing more of a divergence in sequences than
observed in longer than 6000 years. This means that one in 300
individuals would have to die from having mutations in this region.
This seems like a high figure for a region that appears to be largely
without function. It is interesting that this same biologist feels
that 9/10 of the mutations to coding regions of DNA are neutral. This
makes the coding regions of DNA less constrained than the apparently
functionless control region of the mitochondrial DNA!